| Summary: | 碩士 === 元智大學 === 資訊管理學系 === 94 === Conventional procedures for drug design have been very expensive and time-consuming. In general, there are four phases regarding such procedures: initiation of molecular structure, optimization of the structure, biochemical investigations, and clinical trials. Each phase may take approximately three to five years to produce a new drug.
Due to the tremendous progresses on information technology during recent years, it is expected to shorten the required research time spent in the early period of the aforementioned development through computer calculation. CADD (Computer Aided Drug Design) is one of the most powerful concepts applied to satisfy such demand. Upon docking simulations, it is allowed to find out the binding sites and orientations between target proteins and drug molecules in several days. This is not only to save the time and the cost used in drug development, but also for us able to understand the structural implications used for further design. However, it is still currently difficult to formularize efficient software to carry out the docking simulations as a standard procedure leading to definite results with high accuracy. Therefore, this study is in attempts to propose a new category of programming, for which the standard effectiveness for docking procedure can be anticipated in the near future.
To initiate such computer simulations, many factors have to be taken into consideration. The first is to decide which algorithms should be applied to perform the job. GA (Genetic Algorithms) and GP (Genetic Programming) seem to be excellent candidates to solve this problem. The next concern is the determination of scoring function, which is appropriate for either GA or GP to generate their scores. As being the best commercially available scoring function with high accuracy and flexibility, XSCORE is used to satisfy this purpose.
In addition, we concentrate our study in the search of binding site(s) between protein and the drug molecule through docking simulations by applying the aforementioned special algorithms and scoring function. At present stage, target protein is regarded as a rigid body, whereas the drug molecule is allowed to be entirely flexible. According to our results, GA and GP can indeed achieve the searching of correct docking sites between target protein and the drug molecules. This finding seems to be critical in giving evidence of the application of our new method in the drug design procedure. Further studies with partially flexible protein regions added into the docking system will be anticipated in the future and thus accelerate the development of effective software for the design of new lead compounds.
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